Q. Is it better to use mitotane or trilostane in dogs with hyperadrenocorticism due to an adrenal tumor?

A. I think the answer to this question depends on the owners' goals. I will assume if we are talking about medical options that surgical options have been ruled out.

If we are looking to simply palliate the clinical signs of hyperadrenocorticism by lowering cortisol concentrations, then I would choose trilostane as the initial medication. Given the functional nature of the tumor, the adrenal enzyme inhibition afforded with trilostane would likely result in normalization of cortisol concentrations and remission of the clinical signs. This would also occur with a lower rate of treatment-related complications when compared with an adrenolytic such as mitotane (o,p'-DDD). Both benign and malignant cortisol-secreting adrenal tumors would be expected to respond to either medication, though obtaining adequate adrenal suppression may require higher doses, increasing the likelihood of a treatment-related complication.

If the goal is to use a medication to control clinical signs and serve as a form of chemotherapy, then mitotane might appear to be a better choice given its adrenolytic action. However, a recent paper suggests that there is no difference in survival times comparing mitotane and trilostane.1

Generally, doses used to ablate an adrenal tumor with mitotane are markedly higher than those used to control hypercortisolemia. For instance, the most common protocol for adrenal ablation uses a dose of 50 mg/kg given orally b.i.d. daily for 30 days, and glucocorticoid and mineralocorticoid replacement therapy is initiated during week 1. In contrast, the protocol for dogs with pituitary-dependent hyperadrenocorticism involves a dose of 50 mg/kg/day for one week followed by 50 mg/kg/week as maintenance therapy. Typically, as we raise the dose of mitotane, we increase the likelihood of side effects, and this was seen in dogs given adrenal ablative doses.2